[HTML][HTML] Fusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified

K Debackere, L Marcelis, S Demeyer… - Nature …, 2021 - nature.com
K Debackere, L Marcelis, S Demeyer, M Vanden Bempt, N Mentens, O Gielen, K Jacobs…
Nature communications, 2021nature.com
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas
with poor prognosis. Up to 30% of PTCL lack distinctive features and are classified as PTCL,
not otherwise specified (PTCL-NOS). To further improve our understanding of the genetic
landscape and biology of PTCL-NOS, we perform RNA-sequencing of 18 cases and validate
results in an independent cohort of 37 PTCL cases. We identify FYN-TRAF3IP2, KHDRBS1-
LCK and SIN3A-FOXO1 as new in-frame fusion transcripts, with FYN-TRAF3IP2 as a …
Abstract
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Up to 30% of PTCL lack distinctive features and are classified as PTCL, not otherwise specified (PTCL-NOS). To further improve our understanding of the genetic landscape and biology of PTCL-NOS, we perform RNA-sequencing of 18 cases and validate results in an independent cohort of 37 PTCL cases. We identify FYN-TRAF3IP2, KHDRBS1-LCK and SIN3A-FOXO1 as new in-frame fusion transcripts, with FYN-TRAF3IP2 as a recurrent fusion detected in 8 of 55 cases. Using ex vivo and in vivo experiments, we demonstrate that FYN-TRAF3IP2 and KHDRBS1-LCK activate signaling pathways downstream of the T cell receptor (TCR) complex and confer therapeutic vulnerability to clinically available drugs.
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